Method, implantable medical device, and system for determining the condition of a heart valve

ABSTRACT

An implantable medical device has an impedance processor that determines impedance data reflective of the transvalvular impedance of a heart valve of a heart during a heart cycle. The determined impedance data are processed by a representation processor that estimates diastolic and systolic transvalvular impedance representations. A condition processor determines the presence of any heart valve malfunction, such as valve regurgitation and/or stenosis, of the heart valve based on the estimated diastolic and systolic transvalvular impedance representations.

CROSS REFERENCE TO RELATED APPLICATIONS

This a division of U.S. patent application Ser. No. 13/131,527, filedMay 5, 2011, which is a 371 Application of International ApplicationPCT/SE2008/00670, filed Nov. 28, 2008.

FIELD OF THE INVENTION

The present invention generally relates to valve conditiondetermination, and in particular to devices and methods for determiningand monitoring the condition and operation of heart valves.

BACKGROUND OF THE INVENTION

The human heart comprises four heart valves controlling the flow ofblood from the atriums to the ventricles and from the ventricles furtheron into the pulmonary or systemic circulation system. The operation ofthe heart valves is critical for the well-being of the subject and anyvalve malfunctions may lead to severe and possibly life-threateningconditions.

Generally, blood flowing incorrectly backwards through a heart valve,i.e. regurgitation, is either a primary valve related problem that mightcause acute heart failure or is a secondary problem in heart failurepatients. If it is a primary valve related problem, i.e. the valve hasruptured or has been damaged, e.g. through infection, valve surgery istypically employed, where the damaged valve is repaired or replaced witha new artificial valve. Any heart failure will then often resolveautomatically once the valve function has been restored.

If it is a secondary problem in heart failure patients, the main sourcefor regurgitation is probably caused by the dilated state of the heart,making it difficult for the valve to close tightly. In this latter case,monitoring valve condition and status may serve as a valuable tool tomonitor heart failure.

Another common heart valve problem is valve stenosis, where the valvekinetics are disturbed making it difficult to close properly or opensufficiently.

There is therefore a need for a tool of monitoring heart valve functionin order to detect any deleterious heart valve effects and/or detectprimary medical conditions manifesting in change in heart valveoperation.

US 2007/0191901 discloses a cardiac resynchronization therapy (CRT)device that is being programmed based on various impedance-relatedparameters. Multi-vector impedance signals associated with dynamicintracardiac impedance are acquired and related to specific time framesof the cardiac cycle to derive indices representative of systolic anddiastolic cardiac performance. The impedance signals are furtheradjusted by static impedance signals associated with pulmonary impedanceas to derive composite indices representative of cardiac performance andpulmonary vascular congestion.

US 2007/0191901 also discusses that aortic valve stenosis can bedetected using an aortic valve function:

$f = \frac{1}{T_{AVO} - \frac{T_{Z}}{\frac{Z}{t}}}$

where T_(AVO) denotes the time of aortic valve opening, T_(Z) denotesthe onset time of positive impedance slope and

$\frac{Z}{t}$

is the first derivative of the impedance signal and is included toaccount for cardiac output. A similar equation can be used forassessment of aortic valve regurgitation using delays in time to aorticvalve closure from the onset of aortic valve opening or from time ofpeak impedance.

SUMMARY OF THE INVENTION

The prior art technique disclosed in US 2007/0191901 requires theidentification of the opening and closing time of the aortic valve.These exact times may be difficult to identify in the impedance data,thereby needing additional sensor equipment, such as recording ofechocardiograms, in order to identify the required times. Theembodiments of the present invention overcome this and other problemswith the prior art technique.

It is a general object of the invention to provide a determination ofheart valve conditions.

It is another object of the invention to provide an implantable medicaldevice capable of monitoring and determining heart valve conditions in asubject.

The above objects are achieved in accordance with the present inventionby an implantable medical device that is connectable to multipleelectrodes that are implantable for applying and applying electricsignals from at least a portion of a heart. An electric signal isapplied, using the electrodes, over at least a portion of the heart anda resulting electric signal is collected from the heart using theelectrodes. The electric signals are processed by an impedance processorfor determining impedance data reflective of the transvalvular impedanceof a heart valve that is being monitored. The impedance data aredescriptive (representative) of the impedance over the valve and thevalve plane during at least one heart cycle to thereby containtransvalvular impedance data samples during both diastole and systole ofthe at least one heart cycle.

A representation processor is implemented for estimating a diastolictransvalvular impedance representation and a systolic transvalvularimpedance representation for the monitored heart valve. The implantablemedical device has a condition processor that determines a condition ofthe heart valve based on the estimated diastolic and systolictransvalvular impedance representations. The condition processorconcludes that the heart valve is operating correctly, i.e. normalcondition, or determines the presence of a valve malfunction, such asvalve regurgitation or stenosis, based on the transvalvular impedancerepresentations.

Depending on implantation site of the electrodes used for signalapplication and/or signal collection, the implantable medical device canmonitor the condition of one or more heart valves in the heart. Theimplantable medical device may therefore potentially determine thepresence of:

-   -   mitral/tricuspid valve stenosis—significant change, i.e.        increase, in diastolic transvalvular impedance but no        significant change in systolic transvalvular impedance;    -   mitral/tricuspid valve regurgitation—significant change, i.e.        decrease, in systolic transvalvular impedance but no significant        change in diastolic transvalvular impedance;    -   aortic/pulmonary valve stenosis—significant change, i.e.        increase, in systolic transvalvular impedance but no significant        change in diastolic transvalvular impedance; and    -   aortic/pulmonary valve regurgitation—significant change, i.e.        decrease, in diastolic transvalvular impedance but no        significant change in systolic transvalvular impedance.

Embodiments offer the following advantages:

-   Allows heart valve condition determination and monitoring without    the usage of any extra, dedicated sensor equipment; and-   Can be used for monitoring any of the four heart valves or a    combination of at least two heart valves.

Other advantages offered by the embodiments will be appreciated uponreading of the below description of the embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic overview of a human subject having an implantablemedical device according to an embodiment and an indicated externalcommunication device.

FIG. 2 is a schematic block diagram of an embodiment of an implantablemedical device.

FIG. 3 is a schematic block diagram illustrating an embodiment of therepresentation processor of the implantable medical device in FIG. 2.

FIGS. 4A-4F illustrate lead configurations that can be used fordetermining transvalvular impedances according to different embodiments.

FIG. 5A is a diagram schematically illustrating a change intransvalvular impedances for the mitral valve and the tricuspid valveduring valve stenosis.

FIG. 5B is a diagram schematically illustrating a change intransvalvular impedances for the mitral valve and the tricuspid valveduring valve regurgitation.

FIG. 6A is a diagram schematically illustrating a change intransvalvular impedances for the aortic valve and the pulmonary valveduring valve stenosis.

FIG. 6B is a diagram schematically illustrating a change intransvalvular impedances for the aortic valve and the pulmonary valveduring valve regurgitation.

FIG. 7 is a diagram schematically illustrating a change in determinedtransvalvular impedance occurring during systole in the case of mitralvalve regurgitation.

FIG. 8 is a schematic illustration of a heart with connecting mainarteries and veins.

FIG. 9 is a flow diagram illustrating a method of determining acondition of a heart valve.

FIG. 10 is a flow diagram illustrating an embodiment of the estimatingstep of the determining method in FIG. 9.

FIG. 11 is a flow diagram illustrating an additional, optional step ofthe determining method in FIG. 9.

FIG. 12 is a flow diagram illustrating additional, optional steps of thedetermining method in FIG. 9.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Throughout the drawings, the same reference characters will be used forcorresponding or similar elements.

The embodiments generally relate to devices and methods for monitoringand determining the condition of a heart valve of a heart in an animalsubject, preferably mammalian subject and more preferably a humansubject.

As is illustrated in FIG. 8, the human heart 10 has four heart valves11, 13, 15, 17. Blood from the systemic circulation system enters theright atrium 12 by the superior vena cava 20 and the interior vena cava22. The blood flows from the right atrium 12 through a first valve, thetricuspid valve 11, into the right ventricle 16. The oxygen depletedblood is pumped by the contractile action of the right ventricle throughthe pulmonary valve 13 to the lungs via the pulmonary artery 26.

Correspondingly, on the left side of the heart 10 blood enters the leftatrium 14 from the pulmonary vein 24. The blood flows from the leftatrium 14 through the mitral valve 15, also denoted bicuspid valve, tothe left ventricle 16. The oxygen rich blood leaves the left ventriclethrough the aortic valve 17 and enters the aorta 28.

The operation of these four heart valves 11, 13, 15, 17 is critical forthe efficient pumping of the blood through the pulmonary and systemiccirculation systems and the well-being of the subject. Medicalconditions and malfunctions can effect these valves 11, 13, 15, 17 andthereby the operation of the heart 10 as whole.

For instance, medical conditions can cause a leakage of blood backwardsthrough a heart valve, i.e. regurgitation. Valve regurgitation may inturn be due to a primary valve problem, such as a valve rupture, whichmay occur due to a localized heart infarct in the area around the muscleanchoring the chordae tendineae attached to the valves, or a valvedamage through an infection. Also secondary problems, such as a dilationof the heart in heart failure patients, may negatively affect the valvesleading to regurgitation.

Another type of medical condition that can affect the valves isstenosis. In stenosis the valves become stiffer and its kinetics isdisturbed causing them not to open sufficiently.

The present invention is an efficient technique for monitoring theoperation of the heart valves and determining whether a negative medicalcondition has occurred to a valve or if there is a worsening of apreviously determined medical condition. The valve condition monitoringand determination can furthermore be conducted by an implantable medicaldevice (IMD) having cardiac leads but does not require any dedicatedheart valve sensors or other equipment. In clear contrast, conventionalcardiac leads having electrodes attached to or positioned close to theheart can be used for generating data that is processed by the IMD forthe purpose of the valve condition monitoring and determination.

As is further described herein, embodiments can be used for monitoringand determining the condition of one of the four heart valves.Alternatively, multiple heart valves and potentially all four valves canbe monitored depending on the number of electrodes used and theirimplantation sites.

FIG. 1 is a schematic overview of a human patient 1 having an IMD 100 astaught herein. In the figure, the IMD 100 is illustrated as a devicethat monitors and/or provides therapy to the heart 10 of the patient 1,such as a pacemaker, cardiac defibrillator or cardioverter. The IMD 100is, in operation, connected to one or more, two in the figure, cardiacleads 310, 320 inserted into different heart chambers, the right atriumand the right ventricle in the figure. The present invention is thoughnot limited to right chamber leads 310, 320 but can also be used inconnection with leads positioned in the left atrium or ventricle of theheart 10. Actually, also non-intracardiac leads, including epicardiacleads can also be used. The IMD 100 must further not necessarily beconnected to two cardiac leads 310, 320 but could alternatively beconnected to a single lead 320 carrying at least one electrode or morethan two cardiac leads 310, 320.

The patient 1 illustrated in FIG. 1 is a human patient 1. However, thepresent invention is not limited thereto, but can also be applied toIMDs 100 implanted in other animals, in particular other mammals.

FIG. 1 also illustrates an external programmer or clinician'sworkstation 200 that can communicate with the IMD 100. As is well knownin the art, such a programmer 200 can be employed for transmitting IMDprogramming commands, using an included transmitter 270, causing areprogramming of different operation parameters and modes of the IMD100. Furthermore, the IMD 100 can upload diagnostic data descriptive ofdifferent medical parameters or device operation parameters collected bythe IMD 100 to a receiver 270 of the programmer 200. Such uploaded datamay optionally be further processed in the programmer 200 before displayto a clinician on a connected display screen 210. In the light of thepresent disclosure, such uploaded data can include the valve conditioninformation determined according to embodiments and other data relatingto heart valve conditions.

FIG. 2 is a schematic block diagram of an IMD 100 according to anembodiment. The IMD 100 comprises an electrode connecting arrangement110 represented by an electrode input/output (I/O) 110 in the figure.

This electrode I/O 110 is, in operation, connectable to multipleelectrodes 312, 314, 322, 324, 342 of which at least one is designed forbeing implanted in or at least in connection with the heart. As aconsequence, at least one of the multiple electrodes 312, 314, 322, 324,342 is arranged on a cardiac lead 310, 320 connectable to the electrodeI/O 110. This further implies that at least one but not all of themultiple electrodes 312, 314, 322, 324, 342 may not necessarily belead-arranged or be implanted in the immediate vicinity of the heart. Anexample of such an electrode 342, is an electrode 342 constituting thewhole or a portion of the case or can of the IMD 100.

As is well known in the art, an implantable lead or catheter 310, 320has a proximal end connectable to the IMD 100 through the electrode I/O110. This IMD-connecting end presents one or more electric terminalsthat are in electric connection with the electrodes 312, 314, 322, 324present on the opposite distal lead end, where the electric connectionis achieved by electric conductors running along the length of the leadbody. The distal lead end with its electrodes 312, 314, 322, 324 is thenprovided in connection with the heart tissue. For this purpose, the lead310, 320 can include a tissue anchoring element, such as a helicalfixation element, though other fixation elements, such as passivefixation elements, including fines, tines, etc., are also common. Thefixation element can indeed constitute one of the electrodes of the lead310, 320, while remaining electrodes can be ring electrodes oftendenoted indifferent electrodes in the art, defibrillation electrode, orthe like.

The IMD 100 is connected to at least one implantable cardiac lead 310,320. The cardiac lead 310, 320 can be an intracardiac lead positioned inany of the chambers of the heart, such as right and/or left atriumand/or ventricle. Alternatively, the lead 310, 320 could be epicardiallypositioned relative the heart, such as in the coronary vein. In the caseof multiple connectable leads 310, 320 the IMD 100 can be connected tomultiple intracardiac or endocardial leads, multiple epicardial leads ora combination of intracardial and epicardial leads. In a preferredembodiment, the IMD 100 and the electrode I/O 110 are connected to aventricular lead 310, such as right ventricular lead and/or coronaryvein lead (left ventricular lead), and an atrial lead 320, such a rightatrial lead and/or a left atrial lead.

A signal generator 120 of the IMD 100 is electrically connected to theelectrode I/O 110 and connectable electrodes 312, 314, 322, 334, 342.The generator 120 generates an electric signal. The electric signal isan alternating current (AC) signal having particular frequencies. Theelectric signal is applicable over at least a portion of a heart in asubject by two electrodes 312, 322 of the multiple connectableelectrodes 312, 314, 322, 324, 342.

In operation, the signal generator 120 generates the electric signalhaving a defined time-dependent voltage/current profile and forwards thesignal to the electrode I/O 110. The electrode I/O 110 directs theelectric signal to the two relevant signal applying electrodes 312, 322to apply the signal over the relevant portion of the heart. As isfurther described herein, this portion of the heart preferablyencompasses the heart valve to be monitored by the IMD 100. If multipleheart valves are to be monitored, the signal generator 120 preferablygenerates a respective electric signal for each of the heart valves.These electric signals may be the same, i.e. having the samevoltage/current profiles and frequencies, or they may be differentelectric signals. A first such electric signal is then applied over afirst pair of connected electrodes 312, 342, whereas at least one secondelectric signal is applied over a different portion of the heart,typically using a different pair of connected electrodes 322, 342. Theat least two electric signals are applied by the respective electrodepairs to the heart, either in parallel or preferably, in order to reduceany interference therebetween, sequentially.

Two electrodes 314, 324 of the multiple connected electrodes 312, 314,322, 324, 342 collect a resulting electric signal, i.e. resulting ACsignal, originating from at least the portion of the heart. Thisresulting signal is due to the applied electric signal from the signalgenerator 120. In the case multiple electric signals where generated bythe signal generator 120 and applied over different portions of theheart, a respective resulting electric signal is preferably collected byrespective electrode pairs for each of the applied electric signals.Thus, for each monitored heart valve a pair of an applied electricsignal and a collected resulting signal is available for the IMD 100. Ina preferred implementation, the collected resulting electric signal orsignals are sensed AC signals.

An impedance processor 130 is electrically connected to the signalgenerator 120 and the electrode I/O 110. The impedance processor 130processes the electric signal generated by the signal generator 120 andthe resulting electric signal collected by the two electrodes 314, 324connected to the electrode I/O 110. In more detail, the processor 130calculates impedance data or signal based on the generated electricsignal, such as based on the current of the electric signal, and theresulting electric signals, e.g. based on the measured voltage of theresulting electric signal. This impedance data is reflective of atransvalvular impedance of a monitored heart valve during at least oneheart cycle.

In the case multiple heart valves are monitored, the impedance processor130 also processes the other applied electric signals from the signalgenerator 120 and the other resulting electric signals collected fromthe heart. The impedance processor 130 uses these other electric signalsfor determining respective impedance data or signal reflective of thetransvalvular impedance of the monitored heart valves during at leastone heart cycle.

Determination of impedance data based on applied and measured electricsignals is well-known in the art and is therefore not further describedherein.

The impedance processor 130 can utilize different filter combinations,such as bandpass filters, in order to obtain the desired impedance databased on the measured voltage of the resulting electric signal and thecurrent of the applied electric signal. The impedance data determined bythe impedance processor 130 can be a complex impedance signal, i.e.comprising a resistive and a reactive component or alternatively animpedance amplitude and phase angle. Alternatively, only the resistiveor reactive component or the impedance amplitude is used as impedancedata.

In a particular embodiment, the impedance processor 130 can determinethe impedance data as average impedance data. In such a case, theelectric signal is applied over the relevant heart portion overmultiple, preferably consecutive, heart cycles. The resulting electricsignal is furthermore measured during multiple heart cycles. Theimpedance data is then the average impedance during the heart cycle,i.e. including both impedance data determined for diastole and impedancedata determined for systole of the heart cycle.

A representation processor 140 is implemented in the IMD 100 connectedto the impedance processor 130. The representation processor 140receives the impedance data from the processor 130 or fetches it from amemory 160 included in the IMD 100 in the case the impedance processor130 has previously stored the data therein. The impedance processor 140estimates a diastolic transvalvular impedance representation and asystolic transvalvular impedance representation based on the impedancedata. The diastolic transvalvular impedance representation isrepresentative of the transvalvular impedance of the monitored heartvalve during diastole, while the systolic transvalvular impedancerepresentation is indicative of the transvalvular impedance originatingfrom the heart valve but during systole of the heart cycle or an averageheart cycle.

The determined transvalvular impedance representations are forwarded toa condition processor 150 implemented in the IMD 100. The conditionprocessor 150 uses the diastolic and systolic transvalvular impedancerepresentations for determining a condition of a monitored heart valve.

The IMD 100 preferably has access to respective reference diastolic andsystolic transvalvular impedance representations, such as from thememory 160. In such a case, the condition processor 150 compares thediastolic transvalvular impedance representation with the referencediastolic transvalvular impedance representation and compares thesystolic transvalvular impedance representation with the referencesystolic transvalvular impedance representations.

The condition processor 150 also determines the valve condition, such asnormal valve operation or valve malfunction, such as valve regurgitationor valve stenosis, if there is a significant difference between areference transvalvular impedance representation and the relevanttransvalvular impedance representations. A significant difference ispresent if the diastolic and/or systolic transvalvular impedancerepresentation differs from the reference diastolic and/or systolictransvalvular impedance representation with more than adiastolic/systolic threshold value. If no significant differences aredetected the condition processor 150 determines a normal valve conditionor operation.

The reference transvalvular impedance representations present in thememory 160 can be pre-defined diastolic and systolic transvalvularimpedance representations indicative of normal and correct valvefunction for the relevant heart valve. Alternatively and preferably, thereference diastolic and systolic transvalvular impedance representationshave previously been determined by the IMD 100 to thereby get IMD- andpatient-specific reference impedance representations. In such a case,the reference transvalvular impedance representations are basicallydetermined in the same way as the diastolic and systolic transvalvularimpedance representations, i.e. involving the operation of the signalgenerator 120, the impedance processor 130 and the representationprocessor 140 as previously described.

The reference transvalvular impedance representations are thenpreferably generated during a period of time when it is confirmed thatno valve regurgitation, stenosis or other valve malfunction is present.This can be confirmed by the patient's physician, e.g. at a patientfollow-up and/or IMD status check visit.

If the condition processor 150 concludes the presence of a tentativedeleterious valve condition in at least one of the monitored heartvalves, diagnostic data representative of the heart condition isgenerated. This data can be entered in the memory 160 for lateruploading to an external communication unit. Alternatively, or inaddition, the data can be directly and wirelessly sent to the externalunit using the transmitter 170 and connected antenna 175 of the IMD 100.If the IMD 100 has an alarm unit capable of sounding an alarm signal orproviding a tactile alarm signal, such unit could run an alarm if thecondition processor 150 detects a severe deterioration of valveperformance as determined based on an analysis of the diastolic andsystolic transvalvular impedance representations.

This sorting of impedance data samples can be conducted solely based onthe impedance data itself. In other words, the sorting of impedance datasamples can be based on the change in transvalvular impedance valuesnaturally occurs in diastole and systole. Thus, the respectivewell-known morphologies in the transvalvular impedance over a heartcycle are used to identify the start and end of diastole and systole.

In an alternative approach the IMD 100 comprises an electrogram or IEGMprocessor 190 for recording an intracardiac electrogram (IEGM) of theheart during the at least one heart cycle over which impedance datasamples are determined. This IEGM processor 190 basically receiveselectric signals collected by its connected electrodes 312, 314, 322,324, 324, preferably from the electrodes 312, 314, 322, 324 of thecardiac leads 310, 320 and originating from the heart. The samplingfrequency of this IEGM data is preferably the same or has at least awell-defined relationship to the sampling frequency of the transvalvularimpedance data. The diastolic and systolic phases of the heart cycle orcycles are typically identified from the IEGM data in a manner wellknown in the art. The start and end of diastole and systole areidentified and impedance data samples coinciding with the start and endof diastole and systole are identified by the representation processor140 using the predefined relationship between sampling frequencies.

The representation processor 140 can therefore sort the impedance datasamples from the impedance processor 130 into diastolic and systolictransvalvular impedance data samples, respectively, based on the IEGMdata from the IEGM processor 190.

As mentioned above, the respective impedance representation ispreferably compared to a respective reference impedance representation.The resulting difference is compared to a threshold value and ifexceeding the threshold value, the IMD 100 indicates that a negativeheart valve condition has been determined. In such implementations, thecondition processor 150 calculates the differences between thetransvalvular impedance representations and the reference impedancerepresentations:

ΔZ _(T) ^(D) =Z _(T) ^(D) −RZ _(T) ^(D)

ΔZ _(T) ^(S) =Z _(T) ^(S) −RZ _(T) ^(S)

where Z_(T) ^(D) denotes the diastolic transvalvular impedancerepresentation, Z_(T) ^(S) denotes the systolic transvalvular impedancerepresentation, RZ_(T) ^(D) denotes the reference diastolictransvalvular impedance representation, RZ_(T) ^(S) denotes thereference systolic transvalvular impedance representation and ΔZ_(T)^(D/S) represents the calculated differences in diastolic/systolicparameters.

The condition processor 150 compares these differences with respectivethreshold values, which may be the same or different, T_(D), T_(S). Itis anticipated by the present invention that the same diastolic andsystolic threshold values could be used regardless of which heart valvethat is being monitored. In such a case, the threshold value coulddefine a percentage value. Thus, a significant change is detected if thedetermined transvalvular impedance representation differs with more thanthe percentage value from the reference transvalvular impedancerepresentation.

In an alternative implementation, each heart valve has its dedicated setof diastolic and systolic threshold values. This is expected to be apreferred implementation as the threshold values will typically bedependent on different factors, such as the particular patient, theimpedance vectors used, the condition and implementation site of theelectrodes, etc.

The actual threshold values can be set by the physician by analyzingtransvalvular impedance data determined by the IMD for multipledifferent heart cycles. The physician can then identify a variance inthe transvalvular representations that reflects normal fluctuationsoriginating from the impedance measurements and may be due to differentpatient factors, such as body posture, heart rate, etc. Based on theanalysis of such normal variations that are not due to any valvemalfunction, the physician can set the thresholds to have desired valuesthat will disregard normal variations but detect significant changes inthe transvalvular impedance arising due to a valve malfunction.

In order to minimize the impact of different external factors on theimpedance determination, such as body posture, patient activity level,etc., the IMD can be configured to perform the measurements once a setof such measurement conditions are met. For instance, the heart rate, asdetermined from the impedance data or the IEGM data, could be defined tobe within an acceptable measurement interval. The posture of the patientcan be determined using an implantable body posture sensor, which iswell-known in the art. Alternatively, the IMD can be programmed toperform the impedance measurement at a time, when the patient isexpected to be resting, such as during night.

In the following, the embodiments are disclosed further in connectionwith determination of particular valve conditions and for specific heartvalves.

The present invention is based on the finding that a closed heart valveresults in higher electric transvalvular impedance than an open valve.The reason for this is that the valve plane, including the valve tissue,has lower conductivity than myocardial tissue and blood. Thus, a closedvalve will increase the impedance when measuring over the valve.

Stenosis of Mitral Valve, Tricuspid Valve

The mitral and tricuspid valves are positioned between the atriums andthe ventricles in the heart, with the mitral valve between the leftatrium and ventricle and the tricuspid valve between the right atriumand ventricle.

FIG. 5A is a diagram illustrating the transvalvular impedance Z_(T)determined according to an embodiment for the mitral valve or thetricuspid valve for a heart cycle. In the diagram, transvalvularimpedance during normal valve condition is indicated by the unbrokenline. As is seen in the figure, the transvalvular impedance for themitral and tricuspid valves decreases significantly when going fromsystole, where the valves are closed, to diastole with the valvesopened.

The condition processor 150 of the IMD 100 determines a tentativestenosis condition of the mitral and/or tricuspid valve if thedifference between the diastolic transvalvular impedance representationand the reference diastolic transvalvular impedance representationexceeds the diastolic threshold value but the difference between thesystolic transvalvular impedance representation and the referencesystolic transvalvular impedance representation does not exceeds thesystolic threshold value.

In other words the condition processor 150 determines the presence ofmitral or tricuspid valve stenosis if: ΔZ_(T) ^(D)=Z_(T) ^(D)−RZ_(T)^(D)>T_(D) and ΔZ_(T) ^(S)=Z_(T) ^(S)−RZ_(T) ^(T)≦T_(S).

In mitral/tricuspid valve stenosis, the kinetics of the heart valve isimpaired as the opening of the valve becomes impeded by the stenosiscondition. Abnormal opening of the mitral/tricuspid valve duringdiastole when blood is to flow and be pumped from the left/right atriumto the ventricle will increase the transvalvular impedance as the valvecannot fully open correctly during diastole. This is indicated by thehatched line in FIG. 5A.

Mitral and tricuspid valve stenosis does not lead to any significantchanges in systolic transvalvular impedance if the stenotic valve can befully closed during systole.

Mitral Valve, Tricuspid Valve Regurgitation

The condition processor 150 of the IMD 100 determines a tentativeregurgitation condition of the mitral and/or tricuspid valve if thedifference between the systolic transvalvular impedance representationand the reference systolic transvalvular impedance representationexceeds the systolic threshold value but the difference between thediastolic transvalvular impedance representation and the referencediastolic transvalvular impedance representation does not exceed thediastolic threshold value.

In other words the condition processor 150 determines the presence ofmitral or tricuspid valve regurgitation if: ΔZ_(T) ^(S)=Z_(T)^(S)−RZ_(T) ^(S)>T_(S) and ΔZ_(T) ^(D)=Z_(T) ^(D)−RZ_(T) ^(D)<T_(D).

In mitral/tricuspid regurgitation the heart valve cannot fully close,thereby being partly open during systole. FIG. 5B is a diagramillustrating the change in mitral/tricuspid transvalvular impedanceduring normal valve operation, unbroken line, and during regurgitation,the hatched line. As the valve cannot fully close during systole, theconductivity over the valve increases and causing a significantreduction in the systolic part of the transvalvular impedance.

In clear contrast, the diastolic transvalvular impedance will not be orwill only be marginally affected by the mitral/tricuspid valveregurgitation. This phenomenon is due to that the opening of themitral/tricuspid valve is not significantly affected by theregurgitation condition, thereby at most only marginally affecting thediastolic portion of the transvalvular impedance.

FIG. 7 illustrates the mitral transvalvular impedance recorded during aheart cycle. The unbroken line represents the transvalvular impedancewithout any heart valve malfunction. The hatched line indicates thetransvalvular impedance for mitral valve regurgitation. The change intransvalvular impedance is mainly seen during systole, while thediastolic transvalvular impedance changes only marginally with mitralvalve regurgitation.

Stenosis of Aortic Valve, Pulmonary Valve

The aortic and pulmonary valves are positioned between the ventriclesand arteries connecting to ventricles and provided for transportingblood exiting the ventricles throughout the body, i.e. the systemiccirculation system, or to the lungs, i.e. the pulmonary circulationsystem. The aortic valve is arranged between the left ventricle and theaorta, while the pulmonary valve is provided between the right ventricleand the pulmonary artery.

FIG. 6A is a diagram illustrating the transvalvular impedance Z_(T)determined according to an embodiment for the aortic valve or thepulmonary valve for a heart cycle. In the diagram, transvalvularimpedance during normal valve condition is indicated by the unbrokenline. As is seen in the figure the transvalvular impedance for theaortic and pulmonary valves increases significantly when going fromsystole, where the valves are open, to diastole with the valves closed.

The condition processor 150 of the IMD 100 determines a tentativestenosis condition of the aortic and/or pulmonary valve if thedifference between the systolic transvalvular impedance representationand the reference systolic transvalvular impedance representationexceeds the systolic threshold value but the difference between thediastolic transvalvular impedance representation and the referencediastolic transvalvular impedance representation does not exceed thediastolic threshold value.

In other words the condition processor 150 determines the presence ofaortic or pulmonary valve regurgitation if: ΔZ_(T) ^(S)=Z_(T)^(S)−RZ_(T) ^(S)>T_(S) and ΔZ_(T) ^(D)=Z_(T) ^(D)−RZ_(T) ^(D)≦T_(D).

In aortic/pulmonary valve stenosis, the kinetics of the heart valve isimpaired as the opening of the valve becomes impeded by the stenosiscondition. Abnormal opening of the aortic/pulmonary valve during systolewhen blood is to flow and be pumped from the left/right ventricle to theconnected artery will result in an increase in transvalvular impedanceduring systole.

It is expected that no significant change in the diastolic transvalvularimpedance will be detectable during aortic/pulmonary valve stenosis ifthe valve can be fully closed during diastole.

Aortic Valve, Pulmonary Valve Regurgitation

The condition processor 150 of the IMD 100 determines a tentativeregurgitation condition of the aortic and/or pulmonary valve if thedifference between the diastolic transvalvular impedance representationand the reference diastolic transvalvular impedance representationexceeds the diastolic threshold value but the difference between thesystolic transvalvular impedance representation and the referencesystolic transvalvular impedance representation does not exceed thesystolic threshold value.

In other words the condition processor 150 determines the presence ofaortic or pulmonary valve regurgitation if: ΔZ_(T) _(D)=Z_(T) ^(D)−RZ_(T) ^(D)>T_(D) and ΔZ_(T) ^(S)=Z_(T) ^(S)−RZ_(T) ^(S)≦T_(S).

In aortic/pulmonary regurgitation the heart valve cannot fully close,thereby contributing to an increased conductivity over the valve planeduring diastole and therefore a decrease in the diastolic transvalvularimpedance.

In clear contrast, the systolic transvalvular impedance will not be orwill only be marginally affected by the aortic/pulmonary valveregurgitation.

Different impedance vectors can generally be used depending on theparticular heart valve that is to be monitored and the cardiac lead orleads connectable to the IMD. FIGS. 4A to 4F illustrates different suchexamples of impedance vectors that advantageously can be used in orderto determine the transvalvular impedance data used herein for the valvecondition determination.

FIG. 4A illustrates an electrode and lead setting that advantageouslycan be used when monitoring the mitral valve. In such a case, a rightatrial lead 310 having at least one electrode 312, 314 is implanted inthe right atrium 12 of the heart 10. A coronary vein lead or coronarysinus lead 330 having at least one electrode 332-338 is provided inconnection with the left ventricle 18 of the heart. The mitraltransvalvular impedance can be determined based on bipolar, tripolar orquadropolar measurements using one or two electrodes 312, 314 of theright atrial lead 310 and one or two electrodes 332-338 of the coronaryvein lead 330. In bipolar measurements, one of the right atrial leadelectrodes 312, 314 and one of the electrodes 332-338 of the coronaryvein lead 330 are used for both applying the electric signal and forcollecting the resulting electric signal. In tripolar measurement, oneof the electrodes 312, 314, 332-338, either at the right atrial lead 310or at the coronary vein lead 330, is used for both signal applicationand signal collection while remaining two electrodes are dedicated forsignal application and signal collection, respectively. Quadropolarmeasurements, as is illustrated in FIG. 4A, uses a pair of signalapplying electrodes 312, 332 on the two cardiac leads 310, 330 andanother pair of signal collecting electrodes 314, 338 on the cardiacleads 310, 330.

The particular electrode setting illustrated in FIG. 4A, with theapplication of the electric signal over the electrodes 314, 338 and thecollection of the resulting signal over the electrodes 312, 332 shouldmerely be seen as an illustrative example. Actually any combination ofat least two electrodes of the two cardiac leads 310, 330 can be used inbipolar, tripolar or quadropolar mitral transvalvular impedancemeasurements.

FIGS. 4B and 4C illustrate two possible electrode and lead arrangementsthat can be used for monitoring the aortic valve. Starting with FIG. 4B,the IMD 100 is in this case connected to a coronary vein lead orcoronary sinus lead 330 having at least one electrode 332, 334. Bipolaror tripolar aortic transvalvular impedance measurements are available.In bipolar measurements, one of the electrodes 332, 334 of the lead 330is used together with the case/can electrode 342 for both signalapplication and collection. With tripolar measurements, dedicated signalapplication electrode 334 and signal collection electrode 332 are usedfor the lead 330.

In FIG. 4C, the IMD 100 is further connected to a right atrial lead 310having at least one electrode 312, 334. With a tripolar setting, theelectric signal is applied between the case/can electrode 342 and one ofthe electrodes 334 of the coronary vein lead or coronary sinus lead 330and the resulting electric signal is collected over the case/canelectrode 342 and one of the electrodes 312 of the right atrial lead.Alternatively, the electric signal is applied between the can/case andthe right atrial lead 310 and the resulting signal is collected betweenthe can/case and the coronary vein lead 330.

It is expected that for most patients, the arrangement in FIG. 4B may bebetter isolate the aortic transvalvular contribution to the impedancedata than the arrangement of FIG. 4C.

The tricuspid valve can be monitored by an electrode and leadconfiguration as is illustrated in FIG. 4D. Thus, a right atrial lead310 is provided in the right atrium 12 and a right ventricular lead 320is correspondingly provided in the right atrium 16 of the heart 10. Asfor the arrangement in FIG. 4A, bipolar, tripolar or quadropolarimpedance measurements are available using one or two electrodes 312,314 of the right atrial lead 310 and one or two electrodes 322, 324 ofthe right ventricular lead 320. The actual choice of impedance vectorand signal applying and signal collecting electrodes is not thatimportant as long as the electric signal is applied between an electrode312, 314 in the right atrium and an electrode 322, 324 in the rightventricle and the resulting signal is correspondingly collected betweenelectrode 312, 314 in the right atrium and an electrode 322, 324 in theright ventricle.

FIGS. 4E and 4F illustrate two possible arrangements that can be usedfor monitoring the pulmonary valve. In FIG. 4E the IMD 100 is connectedto a right ventricular lead 320 having one or more electrodes 322, 324.Bipolar or tripolar impedance measurements are possible between thecase/can electrode 342 and one or two electrodes 322, 324 in the rightventricle 16.

FIG. 4F illustrates an arrangement that allows tripolar or quadropolarpulmonary transvalvular impedance measurement. In addition to the rightventricular lead 320, the IMD 100 is also connected to a right atriallead 310 having at least one electrode 312, 314. In tripolarmeasurements, the electric signal is applied between the case/canelectrode 342 and a right ventricular electrode 322. The same rightventricular electrode 322 is used together with an electrode 312 of theright atrial lead 310 for collecting the resulting signal.Alternatively, signal application is performed between the rightventricular electrode 322 and the right atrial electrode 312, whilesignal collection involves the can/case electrode 342 and the rightventricular electrode 322.

With quadropolar measurements an electrode 332 of the right ventricularlead 320 is used together with one of the can/case electrode 342 or aright atrial electrode 312 for signal application and another rightventricular lead electrode 324 is used with the other of the can/caseelectrode 342 or a right atrial electrode 312 for signal collection.

The different lead configurations illustrated in FIGS. 4A to 4F may becombined depending on the heart valves that are to be monitored.

Today coronary vein leads are typically used instead of left ventricularleads introduced inside the left ventricle. It is currently within themedical field considered safer for the patient not to have any leadspresent in the left ventricle. However, disregarding any such potentialrisk, the teachings of the present invention can effectively be appliedto a lead configuration where the coronary vein lead is replaced by aleft ventricular lead.

In FIG. 4A, the coronary vein lead 330 has non-limitedly beenillustrated by a so-called multi-electrode lead having a string ofmultiple, typically at least four electrodes 332-338 at differentspatial positions along the lead 330. This is merely used forillustrating that the invention can be used in connection with suchmulti-electrode leads. Thus, any of the leads connectable to the IMDaccording to the arrangements in FIGS. 4A to 4F could be according tothe multi-electrode type or according to a traditional lead type withone or, typically, two electrodes.

Different types of impedance representations can be determined by therepresentation processor 140 of the IMD 100 according to differentembodiments. In a first embodiment, the respective diastolic andsystolic transvalvular impedance waveforms are compared to referencediastolic and systolic transvalvular impedance waveforms or templates.The comparison can be made by calculating the difference between thedetermined waveform and the corresponding reference waveform in asample-by-sample manner. The calculated differences are then added up toget an impedance parameter that is used by the condition processor 150in determining the presence of any heart valve condition. The respectiveimpedance parameters, one for diastole and one for systole, are comparedto predefined threshold values that are either hardcoded in the IMD 100,such as present in the memory 160 or downloaded into the IMD 100 using areceiver 170 with connected antenna 175.

Alternatively, the representation processor 140 identifies pre-definedcharacteristics in the diastolic transvalvular impedance and thesystolic transvalvular impedance. For instance, a global extremetransvalvular impedance value identified among the diastolic impedancesamples and a corresponding global extreme value identified among thesystolic impedance samples could be used as transvalvular impedancerepresentations. In such a case, the global extreme value duringdiastole could be the minimum or maximum value among the diastolictransvalvular impedance samples. The systolic parameter is then themaximum or minimum value among the systolic transvalvular impedancesamples.

The IMD 100 optionally has a quantification processor 180 that isarranged for calculating a quantification parameter from the diastolicand systolic transvalvular impedance representations. Such aquantification parameter may, for instance, be defined as the quotientbetween the above-mentioned minimum (or maximum) diastolic transvalvularimpedance value and the maximum (or minimum) systolic transvalvularimpedance value. The condition processor 150 then determines the currentvalve condition based on a comparison of the calculated quantificationparameter from the quantification processor 180 and a previouslydetermined or received reference quantification parameter. It is evidentfrom the FIGS. 5A to 6B that the quotient between the minimum diastolicimpedance value and the maximum systolic impedance value will bedifferent in stenosis and regurgitation as compared to normal valveoperation for the mitral and tricuspid valves. Correspondingly, thequotient between the maximum diastolic impedance value and the minimumsystolic impedance value can be used for determining the presence ofstenosis or regurgitation of the aortic or the pulmonary valve.

Alternatively, the representation processor 140 calculates one or moreimpedance characteristics or features from the diastolic and systolictransvalvular impedance data. A listing of different preferred impedancecharacteristics follows below. Any one or multiple of thesecharacteristics can be used by embodiments:

-   -   Average impedance—the average impedance during diastole or        systole;    -   Curvature length—the length of the impedance curve during        diastole or systole;    -   Fractionation—is similar to the curvature length but amplitude        normalization in the interval [0, 1] is used;    -   Systolic slope—identifies the maximum first time derivative in        the transvalvular impedance signal during systole; and    -   Peak to peak—takes the difference in the maximum and minimum        transvalvular impedance value during diastole or systole.

Other impedance characteristics derivable from the diastolictransvalvular impedance data and the systolic transvalvular impedancedata could be used instead of or as complement to the above-listedexamples.

The calculated impedance characteristics during diastole or systole arecompared to corresponding reference impedance characteristics calculatedfrom a reference impedance waveform provided in the memory 160 of theIMD 100. In such a case, the reference impedance waveform is preferablyan average waveform determined over multiple heart beats with noindication of any heart valve malfunction.

If the difference exceeds the predefined threshold a tentative heartvalve malfunction may be present as described above.

A further possibility is to have the representation processor 140 tocalculate the first time derivative of the diastolic and systolictransvalvular impedance. The first derivatives are plotted versus therespective regular transvalvular impedance data to form so-calledimpedance loops. Characteristics of the loops can be determined by therepresentation processor 140, such as loop area, loop radius, loopangle. Such characteristics can be calculated using the method describedin U.S. Pat. No. 5,556,419, the teaching of which is hereby incorporatedby reference. Alternatively, morphology comparisons using the calculatedloops and corresponding reference loops determined from the referencediastolic and systolic impedance waveform as described in U.S. Pat. No.5,427,112, the teaching of which is hereby incorporated by reference,can be used.

In an alternative implementation, the representation processor 140comprises a baseline determiner 142 as is illustrated in FIG. 3. Thebaseline determiner 142 processes the transvalvular impedance datasamples from the impedance processor and preferably average data samplesdetermined from measurement over multiple heart cycles. Based on thisprocessing, the baseline determiner 142 calculates a baselinetransvalvular impedance value for the (average) heart cycle. A connectedimpedance converter 144 is implemented for superimposing the diastolicand systolic transvalvular impedance curves, for instance by flippingthe diastolic part. This is conducted by inputting an impedance sampleto a converting function:

Z _(T,i) ^(C)=2×Z _(T) ^(B) −Z _(T,i) ^(D/S)

where Z_(T,i) ^(D/S) transvalvular impedance data of sample i, Z_(T)^(B) indicates the baseline transvalvular impedance determined by thebaseline determiner 142 and Z_(T,i) ^(C) is the converted impedancedata, flipped relative the baseline level.

This converting is preferably performed for each impedance sampledetermined for the diastolic sub-phase of the (average) heart cycle orfor each systolic impedance sample. Following the impedance conversion,both the diastolic and systolic transvalvular impedance samples can besuperimposed and, for example, the representation processor 140 cancalculate the difference between the diastolic and systolictransvalvular impedance samples. This difference is then used asimpedance parameter and is compared by the condition processor with areference impedance parameter.

The units 142 and 144 of the representation processor 140 may beimplemented in hardware, software or combination of hardware andsoftware. The units 142 and 144 may all be implemented in therepresentation processor 140. Alternatively, a distributedimplementation is possible with at least one of the units 142 and 144provided elsewhere in the IMD.

The actual value or values of the thresholds that are used according tothe embodiments can be hardcoded in the IMD at the time of implantation.Alternatively, they are downloaded by the physician following theimplantation time, such as at a patient follow-up meeting. The thresholdvalues may be fixed or can be updated, for instance by the physician bydownloading new, updated threshold values. This may, for instance, beconsidered if the IMD has notified that there is a valve malfunctionbased on the determined impedance data. The physician can then, oncehe/she has concluded that the IMD has determined such a valvemalfunction, perform a more complete investigation of the valvecondition, such as using an ultrasound probe. If the physiciandetermines that no valve malfunction is present even though the IMDsignals this, it might be due to that the local environment around thesignal applying and signal measuring electrodes of the cardiac leads haschanged somewhat, such as through the ingrowth of connective tissue.Such a change in local environment will in turn be captured in thetransvalvular impedance data and will affect the determinedtransvalvular impedance representations. The physician can thereforeupdate threshold values to compensate for this change in electrodeenvironment.

In an alternative and typically more preferred approach, the IMD itself,possibly following that the physician has concluded that no valvemalfunction is present, updates the reference transvalvular impedancerepresentations based on the latest transvalvular impedancerepresentations. The reference transvalvular impedance representationcan, for example, be in the form of an average of several differenttransvalvular impedance representations determined at different timeinstances. A weighted average is typically preferred to thereby moreheavily weight a more recently determined impedance representation ascompared to an outdated impedance representation.

The units 110 to 190 of the IMD 100 can be implemented in hardware,software of a combination of hardware and software.

In the foregoing, the IMD has been described as containing theprocessing functionalities required for determining the transvalvularimpedance data, estimating the diastolic and systolic transvalvularimpedance representations and performing the valve conditiondetermination. FIG. 1 illustrates a system 300 including the IMD 100 anda non-implantable communication and processing device 200, exemplifiedas the programmer or physician's workstation in FIG. 1. The system 300includes the previously described impedance processor 230, therepresentation processor 240 and the condition processor 250. In a firstembodiment all these processors are provided in the IMD 100 asillustrated in FIG. 2. The IMD 100 may then communicate the result ofthe valve condition determination to the receiver 270 of the programmer200, for instance for display to the physician on the display screen210.

A second embodiment of the system 300 has the impedance processor andthe representation processor arranged in the IMD 100. However, thecondition processor 250 is instead arranged in the programmer 200. TheIMD 100 therefore determines the diastolic and systolic transvalvularimpedance representations and transmits them to the receiver 270 of theprogrammer 200. The condition processor 250 uses these transvalvularimpedance representations for determining the condition of a heart valveas previously described.

In a third embodiment of the system 300, the impedance processor isimplemented in the IMD 100, while both the representation processor 240and the condition processor 250 are arranged in the programmer 200. Theimpedance data determined by the impedance processor is thereforeuploaded to the receiver 270 of the programmer 200 for being input tothe representation processor 240.

Finally, a fourth embodiment of the system 300 has the impedanceprocessor 230, representation processor 240 and the condition processor250 implemented in the programmer 200. The IMD 100 therefore merelycollects the raw electric signal and transmits the relevant voltage andcurrent data to the programmer 200 for calculation of the impedance datain the impedance processor 230.

Thus, the processors can be implemented in the IMD 100 or in anon-implantable communication and processing device 200. The operationof the processors is basically the same regardless of implementationsite. Correspondingly, the quantization processor of FIG. 2 may insteadbe provided in the programmer 200 in particular if the conditionprocessor 250 is found in the programmer 200. Correspondingly, the IEGMprocessor may be found in the programmer 200, especially if therepresentation processor 240 and the condition processor 250 arearranged in the programmer 200.

The programmer 200 may also contain data memory in similarity to the IMD100.

If the majority of the processors are provided in the IMD, more of thedata processing is of course performed in the IMD. However, the amountof data sent to the programmer can be kept fairly small, i.e. merelyindicating that a heart valve malfunction has been detected, which valvethat has been effected (can be managed by a 2-bit valve identifier) andpossibly what type of malfunction that has been detected (can be managedby a 2-bit condition identifier in the case of normal, stenosis andregurgitation condition). If the processors instead are provided in thenon-implantable device, the processing of the data is performed therein.The IMD must then, though, transmit fairly large amount of raw data tobe used by the processors.

FIG. 9 is a flow diagram illustrating a method of determining acondition of a valve of a heart in a subject, preferably human subject.The method starts with the steps S1 and S2. Step S1 applies an electricsignal, AC signal, over at least a portion of the heart during at leastone heart cycle. A resulting electric signal, AC signal, is collectedover at least a portion of the heart in step S2. Step S3 determinesimpedance data based on the applied electric signal, such as based onthe current of the of the electric signal, and based on the collectedresulting electric signal, such as based on the voltage of the resultingelectric signal. This impedance data are furthermore reflective of thetransvalvular impedance of a heart valve during at least one heartcycle.

The impedance data are preferably determined based on measurementsconducted during multiple successive or non-successive heart cycles tothereby obtain average impedance data. This in turn reduces the effectof noise and other disturbances that otherwise may have an impact if themeasurements are limited to a single heart cycle. Generally, an averageover 5-10 heart cycles often works really well in terms of noisesuppression.

A next step S4 estimates a diastolic transvalvular impedancerepresentation and a systolic transvalvular impedance representationbased on the impedance data determined in step S3.

The condition of one or more heart valves is determined in step S5 forthe purpose of detecting any valve malfunction or confirming normalvalve condition. The condition determination is furthermore conductedbased on the diastolic and systolic transvalvular impedancerepresentations from step S4

Steps S1 and S2 are conducted by the IMD. The steps S3 to S5 may beperformed in the IMD or may be performed by the programmer.

The procedure illustrated by steps S1 to S5 of FIG. 9 may be conductedonce, such as upon a triggering signal generated by the IMD itself orreceived from an external communication unit, such as programmer.Alternatively, the method is performed periodically or intermittentlyaccording to a defined monitoring schedule. Thus, the method can berepeated once per day, once per week, once per month or with some otherperiodicity.

The transvalvular impedance representations can, as has been previouslydiscussed, average transvalvular impedance values determined based onthe diastolic and systolic impedance data samples for multiple heartcycles. For instance, the global extreme values in the diastolic andsystolic impedance data can be identified and used for calculating aquantification parameter as is illustrated in step S20 of FIG. 11. Thequantification parameter is then compared to a reference quantificationparameter in step S5 of FIG. 9 for the purpose of confirming normalvalve function or determining a valve malfunction.

FIG. 10 is a flow diagram illustrating another embodiment of estimatingimpedance representations. The method continues from step S3 of FIG. 9.A next step S10 determines a baseline transvalvular impedance value for(average) heart cycle. This baseline transvalvular impedance value isused in step S11 for converting the diastolic or the systolictransvalvular impedance data sample to flipped values relative thebaseline level. The method then continues to step S5 of FIG. 9, wherethe converted diastolic (or systolic) transvalvular impedance values arecompared to the systolic (or diastolic) transvalvular impedance valuesfor the purpose of determining a quantification parameter as discussedabove in connection with step S20 of FIG. 11.

FIG. 12 is a flow diagram illustrating additional steps of thedetermining method in FIG. 9. The method continues from step S3 of FIG.9. A next step S30 records an IEGM of the heart, preferably in parallelwith the signal measurements used as a basis for determining thetransvalvular impedance data. The IEGM is used in step S31 for sortingand classifying the impedance data samples into impedance data samplesrelating to diastole of the heart cycle, the multiple heart cycles orthe average heart cycle and those data samples that coincide withsystole. The method then continues to step S4, where the diastolic andsystolic transvalvular impedance representations are determined based onthe sorted impedance data samples.

The valve condition data generated by embodiments is not necessarilylimited to usage as highly valuable diagnostic information to detect anyvalve condition or any other medical condition that causes symptoms ofvalve malfunction. IMD implemented for providing cardiacresynchronization therapy (CRT) to patients having dyssynchrony betweenthe left and right ventricles can benefit from the embodiments. Whenoptimizing the CRT parameters of the IMD, valve regurgitation, inparticular mitral valve regurgitation, may occur in the case onnon-optimal CRT parameters. The valve condition monitoring of theembodiments can therefore be used as a complement during CRT parameteradjustment, in particular AV time and VV time, optimization by detectingthe parameter settings that minimizes or leads to no mitral valveregurgitation.

Although modifications and changes may be suggested by those skilled inthe art, it is the intention of the inventors to embody within thepatent warranted heron all changes and modifications as reasonably andproperly come within the scope of their contribution to the art.

What is claims is:
 1. A method of determining a condition of a valve ofa heart in a subject, said method comprising: applying an electricsignal over a portion of said heart during at least one heart cycle; incomputerized processing circuitry, determining, based on said electricsignal and a resulting electric signal measured over said portion ofsaid heart, impedance data reflective of a transvalvular impedance ofsaid valve during said at least one heart cycle; in computerizedprocessing circuitry, estimating a diastolic transvalvular impedancerepresentation and a systolic transvalvular impedance representationbased on said impedance data in computerized processing circuitry,determining said condition of said valve based on said diastolictransvalvular impedance representation and said systolic transvalvularimpedance representation, and emitting, in electronic form, anindication of said condition of said valve from said computerizedprocessing circuitry.
 2. The method according to claim 1, wherein saidestimating comprises estimating a diastolic average transvalvularimpedance value and a systolic average transvalvular impedance valuebased on said impedance data.
 3. The method according to claim 1,wherein said estimating comprises estimating a minimum transvalvularimpedance value for a diastolic phase of said at least one heart cycleand a maximum transvalvular impedance value for a systolic phase of saidat least one heart cycle based on said impedance data.
 4. The methodaccording to claim 1, wherein said estimating step comprises:determining a baseline transvalvular impedance value for said at leastone heart cycle based on said impedance data; and converting impedancedata corresponding to one of a diastolic phase and a systolic phase ofsaid impedance data according toZ _(T,i) ^(C)=2×Z _(T) ^(B) −Z _(T,i) ^(D/S), where Z_(T,i) ^(C),denotes converted impedance data of data sample ^(i), Z_(T) ^(C) denotessaid baseline transvalvular impedance value and Z_(T,i) ^(D/S) denotesimpedance data of sample ^(i).
 5. The method according to claim 1,further comprising in computerized processing circuitry, determining,based on said diastolic transvalvular impedance representation and saidsystolic transvalvular impedance representation, a quantificationparameter representative of a relation between said diastolictransvalvular impedance representation and said systolic transvalvularimpedance representation, and wherein said determining said conditioncomprises determining said condition of said valve based on saidquantification parameter and a reference quantification parameter. 6.The method according to claim 1, wherein said valve located between anatrium of a first side of said heart and a ventricle of said first sideof said heart and wherein said determining comprises determining aregurgitation condition of said valve if a difference between saidsystolic transvalvular impedance representation and a systolic referencerepresentation exceeds a systolic threshold but a difference betweensaid diastolic transvalvular impedance representation and a diastolicreference representation does not exceed a diastolic threshold.
 7. Themethod according to claim 1, wherein said valve is located between anatrium of a first side of said heart and a ventricle of said first sideof said heart and wherein said determining comprises determining astenosis condition of said valve if a difference between said diastolictransvalvular impedance representation and a diastolic referencerepresentation exceeds a diastolic threshold but a difference betweensaid systolic transvalvular impedance representation and a systolicreference representation does not exceed a systolic threshold.
 8. Themethod according to claim 1, wherein said valve is located between aventricle of said heart and an artery connected to said ventricle andsaid determining step comprises determining a regurgitation condition ofsaid valve if a difference between said diastolic transvalvularimpedance representation and a diastolic reference representationexceeds a diastolic threshold but a difference between said systolictransvalvular impedance representation and a systolic referencerepresentation does not exceed a systolic threshold.
 9. The methodaccording to claim 1, wherein said valve is located between a ventricleof said heart and an artery connected to said ventricle and wherein saiddetermining comprises determining a stenosis condition of said valve ifa difference between said systolic transvalvular impedancerepresentation and a systolic reference representation exceeds asystolic threshold but a difference between said diastolic transvalvularimpedance representation and a diastolic reference representation doesnot exceed a systolic threshold.
 10. The method according to claim 1,further comprising: recording an intracardiac electrogram of said heartover said at least one heart cycle; and in computerized processingcircuitry, identifying, based on said intracardiac electrogram, datasamples of said impedance data comprising diastolic impedance data anddata samples of said impedance data comprising systolic atrial impedancedata.